Idiopathic pulmonary fibrosis (IPF) remains a disease of unknown etiology with a variable put in general poor prognosis. Our hypothesis is that IPF is a disorder of abnormal immunologic regulation in the lung. We view immunologic mechanisms from a broad perspective encompassing all cells and mediators, including neutrophils, mast cells, and mononuclear phagocytes as well as lymphocytes. We will investigate the regulation of inflammation, focusing on how it is perpetuated, what regulates the cessation of inflammation, and what links inflammation and fibrosis. Our program consists of 5 projects and 2 cores. Project 1 is the clinical project and provides the central clinical direction and data base to which all other projects refer. Project 1 has three components: (a) determining what parameters are useful clinically in staging patients with IPF, (b) analyzing surface markers and functional studies of macrophages and lymphocytes for understanding the pathogenesis of IPF, and (c) providing patients and patient material for specialized studies in the projects. The other projects use the bleomycin model of pulmonary fibrosis as well as materials obtained from the clinical project. Project 2 will study the regulation of pulmonary inflammation with a special emphasis on factors which cause cessation or progression of inflammation. Project 3 will examine the triggers of inflammation and the role of oxygen radicals in the perpetuation of inflammation. Project 4 will investigate the link between inflammation and fibrosis with a special emphasis on interactions of mast cells and neutrophils with fibroblasts. Project 5 will evaluate the role of alveolar type II cells in interstitial lung disease based on the hypothesis that the reaction of alveolar epithelial cells to injury is a key determinant in repair versus fibrosis of gas exchange units.